{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lerner S"],"funding":["NICHD NIH HHS","European Research Council","Medical Research Council"],"pagination":["1471-1485"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8460544"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["140(10)"],"pubmed_abstract":["Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus for catecholamine production. Using a conditional mouse model with loss of ASL in catecholamine neurons, we demonstrate that ASL is expressed in dopaminergic neurons in the substantia nigra pars compacta, including the ALDH1A1<sup> +</sup> subpopulation that is pivotal for the pathogenesis of Parkinson disease (PD). Neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. NO supplementation rescues the formation of aggregates as well as the motor deficiencies. Our data point to a potential metabolic link between accumulations of tyrosine and see"],"journal":["Human genetics"],"pubmed_title":["ASL expression in ALDH1A1&lt;sup&gt;+&lt;/sup&gt; neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype."],"pmcid":["PMC8460544"],"funding_grant_id":["818943","MR/T008024/1","U54 HD061221"],"pubmed_authors":["Balmat TJ","Harding CO","Lerner S","Mazkereth R","Ruiz SG","Schulze A","Seminara J","McCarter R","Ryten M","Stricker T","Gallagher RC","Tuchman M","Weisfeld-Adams JD","Wong D","Kreiser T","Berry SA","Bedoyan JK","Izem R","Erez A","Adler L","Gazit E","Eilam R","Waisbren S","Coughlin C","McCandless SE","Spada M","Garcia AC","Ranucci G","Baumgartner MR","Berry G","Gropman A","Hoffmann G","Members of the UCDC","Dionisi-Vici C","Nagamani SCS","Enns G","Le Mons C","Merritt JL","Richesson R","Tsoory M","Burgard P","Baruteau J","Brandis A","Burrage L","Yudkoff M","Mehlman T","Botia JA","Diaz GA"],"additional_accession":[]},"is_claimable":false,"name":"ASL expression in ALDH1A1&lt;sup&gt;+&lt;/sup&gt; neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype.","description":"Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus for catecholamine production. Using a conditional mouse model with loss of ASL in catecholamine neurons, we demonstrate that ASL is expressed in dopaminergic neurons in the substantia nigra pars compacta, including the ALDH1A1<sup> +</sup> subpopulation that is pivotal for the pathogenesis of Parkinson disease (PD). Neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. NO supplementation rescues the formation of aggregates as well as the motor deficiencies. Our data point to a potential metabolic link between accumulations of tyrosine and see","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Oct","modification":"2026-04-08T07:29:58.255Z","creation":"2022-02-11T11:55:11.483Z"},"accession":"S-EPMC8460544","cross_references":{"pubmed":["34417872"],"doi":["10.1007/s00439-021-02345-5"]}}